KR20170102980A - 벤조디아제핀 이량체, 그의 접합체, 및 제조 및 사용 방법 - Google Patents

벤조디아제핀 이량체, 그의 접합체, 및 제조 및 사용 방법 Download PDF

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KR20170102980A
KR20170102980A KR1020177022244A KR20177022244A KR20170102980A KR 20170102980 A KR20170102980 A KR 20170102980A KR 1020177022244 A KR1020177022244 A KR 1020177022244A KR 20177022244 A KR20177022244 A KR 20177022244A KR 20170102980 A KR20170102980 A KR 20170102980A
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alkyl
substituted
mmol
independently
formula
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KR1020177022244A
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Korean (ko)
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용 장
이바르 엠. 맥도널드
나이두 에스. 초우다리
트람 엔. 후인
로버트 엠. 보르질레리
산지브 강와르
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브리스톨-마이어스 스큅 컴퍼니
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Publication of KR20170102980A publication Critical patent/KR20170102980A/ko

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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/68Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
    • A61K47/6835Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
    • A61K47/6843Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a material from animals or humans
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/68Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
    • A61K47/6835Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
    • A61K47/6849Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a receptor, a cell surface antigen or a cell surface determinant
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D487/00Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04Ortho-condensed systems
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D519/00Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/30Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K5/00Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/06Dipeptides
    • C07K5/06008Dipeptides with the first amino acid being neutral
    • C07K5/06017Dipeptides with the first amino acid being neutral and aliphatic
    • C07K5/06034Dipeptides with the first amino acid being neutral and aliphatic the side chain containing 2 to 4 carbon atoms
    • C07K5/06052Val-amino acid
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/70Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/76Antagonist effect on antigen, e.g. neutralization or inhibition of binding

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Immunology (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Molecular Biology (AREA)
  • Genetics & Genomics (AREA)
  • Biophysics (AREA)
  • Biochemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Cell Biology (AREA)
  • Zoology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Peptides Or Proteins (AREA)
  • Medicinal Preparation (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
KR1020177022244A 2015-01-14 2016-01-13 벤조디아제핀 이량체, 그의 접합체, 및 제조 및 사용 방법 KR20170102980A (ko)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US201562103157P 2015-01-14 2015-01-14
US62/103,157 2015-01-14
US201562215928P 2015-09-09 2015-09-09
US62/215,928 2015-09-09
PCT/US2016/013136 WO2016115191A1 (en) 2015-01-14 2016-01-13 Benzodiazepine dimers, conjugates thereof, and methods of making and using

Publications (1)

Publication Number Publication Date
KR20170102980A true KR20170102980A (ko) 2017-09-12

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KR1020177022244A KR20170102980A (ko) 2015-01-14 2016-01-13 벤조디아제핀 이량체, 그의 접합체, 및 제조 및 사용 방법

Country Status (19)

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US (4) US9527871B2 (es)
EP (1) EP3245213B1 (es)
JP (1) JP6498773B2 (es)
KR (1) KR20170102980A (es)
CN (1) CN107428780B (es)
AU (1) AU2016206798A1 (es)
BR (1) BR112017014599A2 (es)
CA (1) CA2973354A1 (es)
CL (1) CL2017001824A1 (es)
CO (1) CO2017008078A2 (es)
EA (1) EA201791550A1 (es)
ES (1) ES2783624T3 (es)
IL (1) IL253402A0 (es)
MX (1) MX2017009145A (es)
PE (1) PE20171184A1 (es)
SG (1) SG11201705646XA (es)
TW (1) TW201632531A (es)
WO (1) WO2016115191A1 (es)
ZA (1) ZA201704738B (es)

Families Citing this family (27)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2016115201A1 (en) * 2015-01-14 2016-07-21 Bristol-Myers Squibb Company Heteroarylene-bridged benzodiazepine dimers, conjugates thereof, and methods of making and using
US9504694B2 (en) 2015-03-19 2016-11-29 Cellerant Therapeutics, Inc. Isoquinolidinobenzodiazepines
WO2018048975A1 (en) 2016-09-09 2018-03-15 Bristol-Myers Squibb Company Use of an anti-pd-1 antibody in combination with an anti-mesothelin antibody in cancer treatment
WO2018053552A2 (en) * 2016-09-19 2018-03-22 Cellerant Therapeutics, Inc. Isoquinolidinobenzodiazepines
EP3522932A4 (en) * 2016-10-10 2020-06-24 Cellerant Therapeutics, Inc. ISOCHINOLIDINOBENZODIAZEPINE (IQB) -1 (CHLORMETHYL) -2,3-DIHYDRO-1-H-BENZO [E] INDOL (CBI) DIMERS
US10398783B2 (en) 2016-10-20 2019-09-03 Bristol-Myers Squibb Company Antiproliferative compounds and conjugates made therefrom
CA3050262A1 (en) 2017-01-25 2018-08-02 Immunogen, Inc. Methods of preparing cytotoxic benzodiazepine derivatives
US20180346488A1 (en) * 2017-04-20 2018-12-06 Immunogen, Inc. Cytotoxic benzodiazepine derivatives and conjugates thereof
EP3668545A2 (en) 2017-08-16 2020-06-24 Bristol-Myers Squibb Company Prodruggable antibodies, prodrugs thereof, and methods of use and making
GB201714115D0 (en) * 2017-09-04 2017-10-18 Femtogenix Ltd Cytotoxic agents
CA3126646A1 (en) 2017-09-29 2019-04-04 Daiichi Sankyo Company, Limited Antibody-pyrrolobenzodiazepine derivative conjugate
CN113444111A (zh) * 2018-05-29 2021-09-28 尹图赛利有限公司 新型苯二氮杂䓬衍生物及其用途
AU2019370859B2 (en) * 2018-10-31 2023-09-21 Intocell, Inc. Fused heterocyclic benzodiazepine derivatives and uses thereof
WO2020100954A1 (ja) 2018-11-14 2020-05-22 第一三共株式会社 抗cdh6抗体-ピロロベンゾジアゼピン誘導体コンジュゲート
LT3886914T (lt) 2018-11-30 2023-05-25 Bristol-Myers Squibb Company Antikūnas, apimantis lengvosios grandinės c gale esantį glutamino turintį prailginimą, jo konjugatus ir metodus bei panaudojimo būdus
WO2020123425A2 (en) 2018-12-12 2020-06-18 Bristol-Myers Squibb Company Antibodies modified for transglutaminase conjugation, conjugates thereof, and methods and uses
GB201901197D0 (en) 2019-01-29 2019-03-20 Femtogenix Ltd G-A Crosslinking cytotoxic agents
CA3191804A1 (en) 2019-03-25 2020-10-01 Daiichi Sankyo Company, Limited Anti-her2 antibody-pyrrolobenzodiazepine derivative conjugate
US20220168440A1 (en) 2019-03-25 2022-06-02 Daiichi Sankyo Company, Limited Antibody-pyrrolobenzodiazepine deprivative conjugate
KR20210143839A (ko) 2019-03-27 2021-11-29 다이이찌 산쿄 가부시키가이샤 항체-피롤로벤조디아제핀 유도체 콘주게이트와 parp 저해제의 조합
WO2020251878A1 (en) 2019-06-11 2020-12-17 Bristol-Myers Squibb Company Anti-ctla4 antibody prodruggable (probody) at a cdr position
WO2021055306A1 (en) 2019-09-16 2021-03-25 Bristol-Myers Squibb Company Dual capture method for analysis of antibody-drug conjugates
CN117425501A (zh) 2021-01-13 2024-01-19 纪念斯隆凯特琳癌症中心 抗体-吡咯并苯二氮䓬衍生物缀合物
CN113372245B (zh) * 2021-06-17 2023-01-13 仪征市海帆化工有限公司 一种n-苯甲酰基-o,o-对甲苯磺酰基-二乙醇胺的合成方法
WO2023037237A1 (en) * 2021-09-09 2023-03-16 Wavelength Enterprises Ltd Process for the preparation of remimazolam
CA3234692A1 (en) * 2021-09-30 2023-04-06 Ajinomoto Co., Inc. Conjugate of antibody and functional substance or salt thereof, and antibody derivative and compound used in production of the same or salts thereof
AU2022401024A1 (en) 2021-11-30 2024-05-16 Daiichi Sankyo Company, Limited Protease-cleavable masked antibodies

Family Cites Families (41)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1109812B1 (en) 1998-08-27 2005-05-04 Spirogen Limited Pyrrolobenzodiazepines
EP2357006B1 (en) 2002-07-31 2015-09-16 Seattle Genetics, Inc. Drug conjugates and their use for treating cancer, an autoimmune disease or an infectious disease
GB0226593D0 (en) 2002-11-14 2002-12-24 Consultants Ltd Compounds
GB0416511D0 (en) 2003-10-22 2004-08-25 Spirogen Ltd Pyrrolobenzodiazepines
GB0404578D0 (en) 2004-03-01 2004-04-07 Spirogen Ltd Pyrrolobenzodiazepines
GB0404577D0 (en) 2004-03-01 2004-04-07 Spirogen Ltd Pyrrolobenzodiazepines
PL2270010T3 (pl) 2004-03-01 2012-07-31 Medimmune Ltd Pochodne 11-hydroksy-5h-pirolo[2,1-c][1,4]benzodiazepin-5-onu jako kluczowe związki pośrednie do otrzymywania c2 podstawionych pirolobenzodiazepin
WO2005085260A1 (en) 2004-03-09 2005-09-15 Spirogen Limited Pyrrolobenzodiazepines
DK1879901T3 (da) 2005-04-21 2010-05-03 Spirogen Ltd Pyrrolobenzodiazepiner
KR20080056167A (ko) 2005-09-26 2008-06-20 메다렉스, 인코포레이티드 씨디70에 대한 인간 모노크로날 항체
PL1960434T3 (pl) 2005-12-08 2012-12-31 Squibb & Sons Llc Ludzkie przeciwciała monoklonalne przeciw fozylowi-gm1 i sposoby zastosowania antyfukozylu-gm1
DK1813614T3 (da) 2006-01-25 2012-01-23 Sanofi Sa Cytotoksiske midler, der omfatter nye tomaymycinderivater
ES2562790T3 (es) 2007-07-17 2016-03-08 E. R. Squibb & Sons, L.L.C. Anticuerpos monoclonales contra Glipicano-3
DK2019104T3 (da) 2007-07-19 2013-12-16 Sanofi Sa Cytotoksiske midler, der omfatter nye tomaymycinderivater, og terapeutisk anvendelse deraf
KR101554848B1 (ko) 2007-10-01 2015-09-21 브리스톨-마이어스 스큅 컴퍼니 메소텔린에 결합하는 인간 항체 및 이의 용도
GB0813432D0 (en) 2008-07-22 2008-08-27 Spirogen Ltd Pyrrolobenzodiazepines
GB0819095D0 (en) 2008-10-17 2008-11-26 Spirogen Ltd Pyrrolobenzodiazepines
NZ594177A (en) * 2009-02-05 2014-02-28 Immunogen Inc Novel benzodiazepine derivatives
FR2949469A1 (fr) 2009-08-25 2011-03-04 Sanofi Aventis Derives anticancereux, leur preparation et leur application en therapeutique
BR112012026801B8 (pt) 2010-04-15 2021-05-25 Medimmune Ltd conjugados de pirrolobenzodiazepina direcionados, composição farmacêutica, uso dos mesmos para tratamento de uma doença proliferativa ou autoimune e ligante de medicamento
EA024730B1 (ru) 2010-04-15 2016-10-31 Медимьюн Лимитед Пирролбензодиазепиновые соединения, их конъюгаты, фармацевтические композиции, содержащие указанные конъюгаты, и применение указанных конъюгатов
BR112012026410B8 (pt) 2010-04-15 2023-01-31 Spirogen Dev Sarl Composto e conjugado de pirrolobenzodiazepinas e usos dos mesmos
FR2963007B1 (fr) 2010-07-26 2013-04-05 Sanofi Aventis Derives anticancereux, leur preparation et leur application therapeutique
ES2717657T3 (es) 2011-02-15 2019-06-24 Immunogen Inc Métodos para la preparación de conjugados
JP6170494B2 (ja) 2011-09-20 2017-07-26 メドイミューン・リミテッドMedImmune Limited ピロロベンゾジアゼピン
CN103987384A (zh) 2011-10-14 2014-08-13 西雅图基因公司 吡咯并苯并二氮杂卓和靶向结合物
US9387259B2 (en) 2011-10-14 2016-07-12 Seattle Genetics, Inc. Pyrrolobenzodiazepines and targeted conjugates
CN110183470A (zh) 2011-10-14 2019-08-30 麦迪穆有限责任公司 吡咯并苯并二氮杂卓
ES2556584T3 (es) 2011-10-14 2016-01-19 Medimmune Limited Pirrolobenzodiazepinas y conjugados de las mismas
EA028457B1 (ru) 2011-10-14 2017-11-30 Медимьюн Лимитед Пирролобензодиазепины
WO2013177481A1 (en) * 2012-05-25 2013-11-28 Immunogen, Inc. Benzodiazepines and conjugates thereof
EP2887965A1 (en) 2012-08-22 2015-07-01 ImmunoGen, Inc. Cytotoxic benzodiazepine derivatives
SI2906248T1 (sl) 2012-10-12 2019-02-28 Medimmune Limited Pirolobenzodiazepini in njihovi konjugati
PT2766048E (pt) 2012-10-12 2015-02-25 Spirogen Sarl Pirrolobenzodiazepinas e conjugados das mesmas
WO2014080251A1 (en) 2012-11-24 2014-05-30 Hangzhou Dac Biotech Co., Ltd. Hydrophilic linkers and their uses for conjugation of drugs to cell binding molecules
WO2014096368A1 (en) 2012-12-21 2014-06-26 Spirogen Sàrl Pyrrolobenzodiazepines and conjugates thereof
WO2014096365A1 (en) 2012-12-21 2014-06-26 Spirogen Sàrl Unsymmetrical pyrrolobenzodiazepines-dimers for use in the treatment of proliferative and autoimmune diseases
US9649390B2 (en) 2013-03-13 2017-05-16 Medimmune Limited Pyrrolobenzodiazepines and conjugates thereof
CN105209077B (zh) 2013-03-13 2019-06-11 麦迪穆有限责任公司 吡咯并苯并二氮杂卓以及其结合物
EP2968596B1 (en) 2013-03-13 2019-03-06 Medimmune Limited Pyrrolobenzodiazepines and conjugates thereof
WO2014174111A1 (en) 2013-04-26 2014-10-30 Pierre Fabre Medicament Axl antibody-drug conjugate and its use for the treatment of cancer

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AU2016206798A1 (en) 2017-08-31
IL253402A0 (en) 2017-09-28
MX2017009145A (es) 2017-11-22
CO2017008078A2 (es) 2017-11-10
PE20171184A1 (es) 2017-08-22
US10112975B2 (en) 2018-10-30
ES2783624T3 (es) 2020-09-17
US20170073357A1 (en) 2017-03-16
US9822144B2 (en) 2017-11-21
CL2017001824A1 (es) 2018-02-09
US9676794B2 (en) 2017-06-13
US9527871B2 (en) 2016-12-27
US20160200742A1 (en) 2016-07-14
ZA201704738B (en) 2019-02-27
US20180079781A1 (en) 2018-03-22
CN107428780A (zh) 2017-12-01
EA201791550A1 (ru) 2017-11-30
SG11201705646XA (en) 2017-08-30
BR112017014599A2 (pt) 2018-01-16
EP3245213B1 (en) 2020-03-04
WO2016115191A1 (en) 2016-07-21
US20170233436A1 (en) 2017-08-17
EP3245213A1 (en) 2017-11-22
CA2973354A1 (en) 2016-07-21
TW201632531A (zh) 2016-09-16
JP6498773B2 (ja) 2019-04-10
CN107428780B (zh) 2020-09-04
JP2018503639A (ja) 2018-02-08

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